AZURE-1: Brelovitug Responses Deepen Beyond Week 24 in Chronic Hepatitis D

Brelovitug, an investigational monoclonal antibody against hepatitis B surface antigen (HBsAg), produced continued improvements in hepatitis D virus (HDV) RNA and alanine aminotransferase (ALT) beyond 24 weeks of treatment in adults with chronic hepatitis D (CHD), according to phase 2b data from the AZURE-1 trial presented at AASLD The Liver Meeting 2026.¹

Douglas Dieterich, MD, of the Icahn School of Medicine at Mount Sinai, presented the findings and discussed them in an interview with HCPLive. He described the mechanism simply: HDV relies on HBsAg as its outer coat, so binding HBsAg into antigen-antibody complexes leaves the virus unable to reproduce.

“The longer you use the medication, the better it works,” Dieterich said.

How Did Brelovitug Perform Beyond 24 Weeks in AZURE-1?

The phase 2b portion of AZURE-1 randomized 53 adults with CHD in a 2:2:1 ratio to brelovitug 300 mg subcutaneously once weekly, self-administered at home (n = 21); 900 mg every 4 weeks in clinic (n = 20); or delayed treatment for 24 weeks followed by 300 mg weekly (n = 12).¹ More than half (53%) had cirrhosis, and the trial imposed no exclusions for liver stiffness, bilirubin, albumin, INR, or maximum ALT.

At Week 24, the composite primary endpoint of virologic response and ALT normalization was met by 45% (9/20) of patients receiving 300 mg weekly (P = .003) and 35% (7/20) receiving 900 mg every 4 weeks (P = .024), compared with 0% (0/12) with delayed treatment. Virologic response occurred in 100%, 75%, and 0%, and ALT normalization in 45%, 40%, and 8%, respectively.¹

Responses continued to improve with ongoing treatment. Mirum Pharmaceuticals reported the composite endpoint rose to 55% in both dose groups by Week 48, and HDV RNA below the lower limit of quantification increased from 45% to 80% with weekly dosing and from 10% to 40% with every-4-week dosing.²

What Does Brelovitug Mean for HDV Screening and Treatment?

Through Week 24, mild injection site reactions occurred in 17% of brelovitug-treated participants, and 1 participant reported mild flu-like symptoms.¹ There were no treatment-related serious adverse events, grade 3 or higher adverse events, or discontinuations due to adverse events. Dieterich noted a single serious adverse event later in the trial, a hospitalization to manage ascites.

Dieterich said brelovitug should change the CHD treatment landscape, citing the convenience of weekly or monthly dosing compared with the once-daily bulevirtide (Hepcludex), which received accelerated approval from the US Food and Drug Administration in May 2026 as the first therapy for chronic HDV.³ He added patients in his practice have reported feeling better, stronger, and gaining weight on treatment.

He also highlighted large gaps in HDV screening, as many clinicians, including primary care physicians who manage hepatitis B, do not routinely test for HDV. A recently analysis revelaed fewer than 10% of patients with hepatitis B in New York City had ever been tested for HDV.⁴

“Everybody who’s surface antigen positive should be tested for delta hepatitis,” Dieterich said.

The phase 3 portion of AZURE-1 met its primary endpoint in September 2026, with composite response rates of 56% with 300 mg weekly and 45% with 900 mg every 4 weeks vs 0% with delayed treatment.² Mirum plans to submit a biologics license application in the first half of 2027.²

References:

1. Dieterich D, Yardeni D, Kushner T, et al. Brelovitug monotherapy for the treatment of chronic hepatitis D: results from beyond week 24 treatment in the AZURE-1 phase 2b study. Presented at: The Liver Meeting 2026; November 5-9, 2026; Denver, CO.

2. Hillenbrand A. Brelovitug meets primary endpoint in phase 3 AZURE-1 hepatitis delta trial. HCPLive. Published September 28, 2026. Accessed November 8, 2026. https://www.hcplive.com/view/brelovitug-meets-primary-endpoint-phase-3-azure-1-hepatitis-delta-trial

3. Bulevirtide receives historic first FDA approval for chronic hepatitis delta. HCPLive. Published May 22, 2026. Accessed November 8, 2026. https://www.hcplive.com/view/bulevirtide-historic-first-fda-approval-chronic-hepatitis-delta

4. Kushner T. New phase 2b AZURE-1 data signal progress in chronic hepatitis D treatment, with Tatyana Kushner, MD. HCPLive. Published April 28, 2026. Accessed November 8, 2026. https://www.hcplive.com/view/new-phase-2b-azure-1-data-signal-progress-in-chronic-hepatitis-d-treatment-with-tatyana-kushner-md